The overall goals of the proposed experiments are to examine acute stress regulation of the hypothalamic-pituitary-thyroid (HPT) axis and to determine if models of active behavioral coping can ameliorate stress effects on neuroendocrine systems and behavior. The HPT axis has not been well studied as a stress responsive system, but has important physiological consequences, including changes in mood and affective states. Successful coping with stress is necessary to promote individual resiliency and to prevent pathological outcomes associated with stress exposure. It is essential to determine the neural and endocrine consequences of successful coping. There is little previous work examining the impact of active behavioral coping on acute stress-induced decreases in thyroid hormones. Interestingly we have preliminary evidence that acute inescapable stress can cause a decrease in peripheral thyroid hormones levels and, moreover, that this stress-induced decrease is diminished in animals that can cope with, via escaping, the stressor. In this grant application we propose to fully assess the activity of the HPT axis during acute stress, and also determine if active behavioral coping strategies prevent stress-induced decreases in HPT axis activity. The two active behavioral coping strategies that we will focus on are 1. Escaping/controlling the stressor (tail-shock) via an operant response and 2. Performance of a displacement behavior (chewing a wooden stick) during the stressor. In addition, we propose to determine the effects of active behavioral coping on social behaviors that are negatively impacted by stress. Finally, the hypothalamic-pituitary-adrenal (HPA) axis is a very well characterized stress-responsive system, but the impact of the performance of a displacement behavior on stress activation of the HPA axis has not been completely characterized. To determine stress- induced changes in the HPA and HPT axes, we will measure both circulating hormone levels and hypothalamic mRNA and hnRNA levels. The experimental animal for the proposed studies is the adult male rat. The HPT axis has known peripheral and central effects, and well-defined neuroanatomical inputs. Despite this knowledge, this neuroendocrine system is relatively unstudied within the context of stress responsiveness. The studies proposed in this R03 application will confirm and extend our understanding of the HPT axis responses to stress and active behavioral coping. Further, they will provide the foundation for future studies characterizing the neural underpinnings of stress regulation of the HPT axis and determining how this neural regulation is altered by active behavioral coping. PUBLIC HEALTH RELEVANCE: Successful coping with life stressors is critical for preventing negative health outcomes caused by stress exposure. Rodent models have analogous response systems to people and can be used to directly identify negative consequences of stress and also consequences of successful stress coping. Identification of these systems may provide insight into successful stress-coping strategies, interventions, and therapies for humans.